The compound morphine or (-)7,8-didehydro-4,5.alpha.-epoxy-17-methylmorphinan-3,6.alpha.-diol, is a phenanthrene derivative that exhibits the general structure as shown in FIG. 6.
Morphine is a centrally acting narcotic analgesic that acts as an agonist primarily at mu, kappa and perhaps delta receptors in the central nervous system. By acting on these receptors, morphine causes analgesia and anesthesia as a result of a receptor-mediated central action on pain perception, together with a receptor-medicated modulatory effect on the central transmission of noxious sensation. Some side effects caused by morphine include drowsiness, respiratory depression and euphoria.
Various morphine compositions are known in the pharmaceutical arts. For example, morphine sulfate is one of the most commonly prescribed morphine compositions. Other morphine compositions such as morphine tartrate and morphine lactate are disclosed in U.S. Pat. No. 5,880,132 issued to Hill and U.S. Pat. No. 5,378,474 to Morella et al. for the treatment and prevention of pain or nociception. Some polar compositions of morphine including morphine-3-glucuronide and morphine-6-glucuronide are disclosed in U.S. Pat. No. 5,629,011 to Illum. While these references discuss different pharmaceutical compositions of morphine, none disclose morphine gluconate or a chemically modified equivalents thereof.
Morphine has been used for a variety of clinical indications. Some examples of such indications include analgesia, for treatment of acute and chronic pain, anesthesia during surgery and to allay anxiety during acute pulmonary edema.
Several delivery routes have been utilized for administering morphine. These routes include oral, injectable, buccal and intranasal administration. For example, oral and injectable morphine sulfate are commonly prescribed for cancer pain. Oral and injectable morphine sulfate are available from Abbott Pharmaceuticals Inc., USA.
Other more desirable delivery routes have been investigated. For example, intranasal delivery of morphine has shown potential for rapid onset and duration of action. Further, intranasal administration offers minimal delays in absorption, is not as invasive as intravenous delivery and achieves therapeutically effective amounts of the drug in plasma. For example, intranasal delivery of morphine is disclosed in U.S. Pat. No. 5,629,011 to Illum and U.S. Pat. No. 4,464,378 to Hussain for the treatment of chronic and acute pain. The entire disclosure of U.S. Pat. No. 5,629,011 and U.S. Pat. No. 4,464,378 is herein incorporated by reference. While these references discuss the benefits of intranasal delivery of morphine, there is no consideration of using morphine gluconate or chemical equivalent thereof as an analgesic or anesthetic.
Based on the foregoing, there is a need for effective morphine compositions and methods for eliciting analgesic and anesthetic responses. The morphine compositions and methods of the present invention include morphine gluconate or chemical equivalent thereof.